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Upregulation of Hippocampal MAPK ERK /NFκB Signaling Accounts for the Opioid Receptor‐dependent Incitement of Cognitive Impairment in Septic Rats
Author(s) -
Abuiessa Salwa A.,
Ayieng’a Evans O.,
Elblehi Samar S.,
ElGowilly Sahar M.,
Afify Elham A.,
ElMas Mahmoud M.
Publication year - 2022
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2022.36.s1.r3338
Subject(s) - medicine , sepsis , (+) naloxone , hippocampal formation , hippocampus , morris water navigation task , opioid , anesthesia , pharmacology , receptor
Earlier reports indicate that morphine provokes cognitive and circulatory defects caused by sepsis. Pharmacologic, histopathologic, and molecular studies were employed in this communication to implicate inflammatory pathways of the hippocampus in this clinically relevant sepsis‐morphine interaction. Sepsis was induced with cecal ligation and puncture and behavioral studies were undertaken 24 hr later. The data showed that the subcutaneous treatment of septic rats with morphine (7 mg/kg, 6 and 24 hr prior to sepsis) caused significant (i) decreases in systolic blood pressure measured by the tail‐cuff plethysmography, and (ii) impairment in cognitive function as revealed by Morris water maze test, new object recognition test, and Y maze test. Such hemodynamic and behavioral anomalies were substantially obliterated after blockade of opioid receptors or inhibition of TNFα with naloxone (0.5 mg/kg) and infliximab (6 mg/kg), respectively. The improvement in cognitive function caused by naloxone or infliximab was paralleled with dramatic falls in serum IL‐1β and diminution in neuronal degeneration and necrosis seen in hippocampal tissues. Immunohistochemical studies revealed that the heightened hippocampal expression of MAPK ERK and NFκB observed in the sepsis/morphine‐challenged rats was remarkably reduced upon treatment with naloxone or infliximab. These findings incriminate opioid receptors in the amplified hemodynamic and behavioral sequalae of sepsis and suggest a therapeutic potential for the downregulation of hippocampal MAPK ERK /NFκB cascade in offsetting the exaggerated responsiveness to the sepsis/morphine insult.